This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Biophysical investigations are proposed to elucidate key aspects of the functional interactions between proteins and lipids in biological membranes. Membrane proteins are an important frontier within not only biochemistry, but science generally. Membrane protein function has crucial implications for cell physiology and the regulation of biological function. A key goal of this project will be to develop and advance experimental methods in solid-state NMR spectroscopy and fluorescence microscopy that are needed for addressing the mechanisms by which proteins and lipids interact within biological membranes. Due to the complexity of biological membranes, the projects proposed here will, initially, make use of judiciously designed model systems that consist of small, hydrophobic protein domains and that will pave the way for studies of more complex systems. We then will extend the methods to investigate and characterize a prototype system of greater complexity, the membrane-anchored cytochrome P450 enzyme. The model systems provide two means for setting the stage: they allow understanding and insight into fundamental molecular interactions;and they lend themselves toward the development of experimental techniques that then become available for application to other (larger) systems, such as the complexes of P450 with membrane-bound reaction partners, and beyond. Tangible benefits for health care may accrue in two ways: The model and prototype systems themselves may suggest new strategies for membrane-based interventions in diagnostic or clinical medicine. Furthermore, the general membrane principles that are learned may be applied to medical issues in membrane biology.